Significance A non-human primate model for HHV-8 infection will be significant for elucidating mechanisms of viral pathogenesis and the development of antiviral drugs and vaccines. Pilot studies in this project indicate that a low-level persistent infection can be obtained in rhesus macaques inoculated with HHV-8 particles. Objectives Human herpes virus type-8 (HHV-8), also known as Kaposi's sarcoma herpes virus (KSHV) is a newly identified human virus that has been implicated in Kaposi's sarcoma and other neoplasms (e.g., body cavity lymphoma) in HIV-infected AIDS patients. An animal model to study mechanisms of viral pathogenesis and to test anti-viral drugs and vaccines is not available for HHV-8. Accordingly, a pilot study was performed to determine whether rhesus macaques could be infected with HHV-8. Results The virus inoculum consisted of virus obtained from the culture medium of a human B-cell line which can be induced to produce HHV-8 particles. Two healthy juvenile macaques were inoculated by the intravenous route with this inoculum. Analysis of peripheral blood lymphocytes by polymerase chain reaction (PCR), with viral-specific primers, revealed that viral DNA was present for over one year after infection. Both animals have remained healthy with no signs of neoplasia. Two additional juvenile macaques, chronically infected with pathogenic SIVmac251, were inoculated with HHV-8 by the intravenous route with the same inoculum as above. Each of these SIV carriers contained HHV-8 DNA as demonstrated by PCR analysis of peripheral blood lymphocytes. Within one year, both of these animals developed a fatal AIDS-like disease. Necropsy analysis did not reveal endothelial cell abnormalities or neoplasia. Future Directions Two experiments are planned to continue efforts at developing a non-human primate model for HHV-8 infection and (potential) pathogenesis. First, newborn rhesus macaques will be inoculated with HHV-8; newborn animals are generally immunologically immature and may be more susceptible to infection. Second, adult Callicebus (titi) monkeys, a New World species, will be inoculated with HHV-8; the idea for this pilot study is based on the observation that certain herpes viruses from Old World primates cause disease in New World primates. KEY WORDS HHV-8, vaccine FUNDING UC Discretionary Funds